PONE-D-23-37340Perinatal mortality after Chornobyl in contaminated regions of UkrainePLOS ONE

Dear Dr. Körblein,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. In other words, congratulations! Both reviewers felt your paper had merit but needed a little more work before final acceptance. I think perhaps the two most important issues concern the fact that Sr-90 is not the only radioisotope of interest given that Cs-137 likely also  had a significant contribution to the received dose. Please explore this question as best you can. And of course there were many other isotopes released some of which have been well documented to be important for public health (e.g. iodine isotopes). Including some discussion beyond Sr likely broadens the audience for your paper.The other issue that must be addressed concerns the position of the Rivne Oblast in the analyses. There have been a number of papers on related topics indicating that because of soil type and other factors, Rivne Oblast may not be a control area and in fact might be considered to be a region of significant dose. Perhaps you can explore this question in your analyses. I think this could be very helpful for the broader discussion. 

There are several other issues that are presented by reviewer #2 that should be addressed in your revision. For example, is quite common to include as co-authors people who have contributed unpublished data. I am not sure to what extent this should be considered here. It is not a simple issue but please reflect on this as you prepare your revision. And of course, should you have any questions, feel free to contact me directly. 

Please submit your revised manuscript by Feb 10 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Tim A. Mousseau

Academic Editor

PLOS ONE

Journal requirements:

1. When submitting your revision, we need you to address these additional requirements.

Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at 

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and 

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf.

2. We note that you have referenced (ie. 7. Omelyanets N et al. [7]) which has currently not yet been accepted for publication. Please remove this from your References and amend this to state in the body of your manuscript: (ie “Omelyanets N et al. [Unpublished]”) as detailed online in our guide for authors

http://journals.plos.org/plosone/s/submission-guidelines#loc-reference-style 

3. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. 

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have excellently inferred based on theroretical modelling that the observed increase in perinatal mortality in the 1990s may be a late effect of incorporated radioactive strontium-90 on the immune system of pregnant women. Though the results are not fully conclusive and further studies may be warranted in future, the manuscript will lay the foundation for such research and is hence acceptable for publication as it is. The reviewer congratulates the author for this thought provoking study.

Reviewer #2: It is self-evident that the author is a competent investigator and has produced a thorough report. However, from a biologic point of view, statistical analyses cannot improve data flaws nor interpretation flaws. We believe that the report focuses attention on an important issue - death as an end point of radiation "sickness" "syndrome". Incorporated radionuclides impact physiology and homeostasis and may enhance lethal effects of extemporaneous causes rendering infants more label, ultimately reflected in mortality. Incorporation of radionuclides is gradual by women, pregnant women, and by their infants. Also, noteworthy is that at the time of the reported peak of mortality, in Ukraine, the definitions of stillbirth-livebirth were modified. In summary, we believe this report is important and that the author or authors can easily restructure the presentation. In this spirit we offer the following suggestions.

1. The author indicates that the analysis of the data provided by Dr. N. Omelyanets was to be published jointly. The author submits this report without Dr. N. Omelyanets and instead acknowledges his contribution. A comment clarifying this discrepancy would be welcome.

2. The control data includes Rivne oblast which in turn includes Rivne Polissia. This region is considered by multiple experts to be among the most polluted by Chornobyl radionuclides. Furthermore, the soils in Rivne Polissia have the highest transfer index of radionuclides from soil to biota (see reports by Likhtarev et al.). This fact enhances the biologic impacts of incorporated radionuclides in this area. Rivne Polissia should not be included as a component of a "control" population.

3. The incorporation of radionuclides represents admixtures. Generally, the proportion of incorporated Cs-137 is greater than of Sr-90. The reasons why the author is entirely focused on one radionuclide is at best questionable. Perhaps, there are good reasons for this emphasis and if so, they should be stated more clearly.

4. The report concerns mortality and, as is stands, it almost conveys the notion of a statistical exercise which belongs in a supplement.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Perinatal mortality after Chornobyl in contaminated regions of Ukraine

PONE-D-23-37340R1

Dear Dr. Körblein,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Congratulations. This is a valuable contribution to this field and you are to be commended for your painstaking effort to unravel the possible causes of variation in the data. 

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Tim A. Mousseau

Academic Editor

PLOS ONE